Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice
Open accessAbstract
Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators.
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The signaling mechanisms of hydrogen peroxide in ECs lead to the increased activity of eNOS and other enzymes.
“The signaling mechanisms of hydrogen peroxide in ECs (941) lead to the increased activity of eNOS and other enzymes (121, 141, 193, 251, 815, 940).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [941]
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- Authors
- Thoonen, R., Cauwels, A., Decaluwe, K., Geschka, S., Tainsh, R. E., Delanghe, J., Hochepied, T., De Cauwer, L., Rogge, E., Voet, S., Sips, P., Karas, R. H., Bloch, K. D., Vuylsteke, M., Stasch, J.-P., Van de Voorde, J., Buys, E. S., & Brouckaert, P.
- Affiliations
- Ghent University (BE)
- Bayer (Germany) (DE)
- Massachusetts General Hospital (US)
- Ghent University Hospital (BE)
- Tufts Medical Center (US)
- Corresponding author
- Thoonen, Robrecht
- Brouckaert, Peter
- ORCID
- Venue
- Nature Communications
- Published
- 2015-10-07
- Volume
- 6
- Issue
- 1
- Pages
- 8482-8482
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4699393
- OpenAlex
- W2229701246
- Cited by
- 77
- References
- 61
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 2 · 2023: 9 · 2022: 5 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 15 · 2017: 7 · 2016: 10
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- American Heart Association
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- National Institutes of Health
- National Eye Institute (R01EY022746)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- soluble guanylate cyclase, nitric oxide, cinaciguat, sGC activators, oxidative stress, hypertension, smooth muscle relaxation, platelet aggregation, shock, cardiovascular disease
- MeSH terms
- Soluble Guanylyl Cyclase, Animals, Benzoates, Blood Pressure, Cardiovascular System, Guanylate Cyclase, Heme, Hypertension, Hypotension, Mice, Transgenic, Muscle, Smooth, Vascular, Nitric Oxide, Platelet Aggregation, Tumor Necrosis Factor-alpha, Receptors, Cytoplasmic and Nuclear, Oxidative Stress, Mice, Gene Knock-In Techniques
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